Differential pathways for interleukin-1β production activated by chromogranin A and amyloid β in microglia

Zhou Wu, Li Sun, Sadayuki Hashioka, Sheng Yu, Claudia Schwab, Ryo Okada, Yoshinori Hayashi, Patrick L. McGeer, Hiroshi Nakanishi

研究成果: Contribution to journalArticle査読

59 被引用数 (Scopus)

抄録

Although chromogranin A (CGA) is frequently present in Alzheimer's disease (AD), senile plaques associated with microglial activation, little is known about basic difference between CGA and fibrillar amyloid-β (fAβ) as neuroinflammatory factors. Here we have compared the interleukin-1β (IL-1β) production pathways by CGA and fAβ in microglia. In cultured microglia, production of IL-1β was induced by CGA, but not by fAβ. CGA activated both nuclear factor-κB (NF-κB) and pro-caspase-1, whereas fAβ activated pro-caspase-1 only. For the activation of pro-caspase-1, both CGA and fAβ needed the enzymatic activity of cathepsin B (CatB), but only fAβ required cytosolic leakage of CatB and the NLRP3 inflammasome activation. In contrast, fAβ induced the IL-1β secretion from microglia isolated from the aged mouse brain. In AD brain, highly activated microglia, which showed intense immunoreactivity for CatB and IL-1β, surrounded CGA-positive plaques more frequently than Aβ-positive plaques. These observations indicate differential pathways for the microglial IL-1β production by CGA and fAβ, which may aid in better understanding of the pathological significance of neuroinflammation in AD.

本文言語英語
ページ(範囲)2715-2725
ページ数11
ジャーナルNeurobiology of Aging
34
12
DOI
出版ステータス出版済み - 12 2013

All Science Journal Classification (ASJC) codes

  • 神経科学(全般)
  • 加齢科学
  • 臨床神経学
  • 発生生物学
  • 老年医学

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